POS0948 PATTERNS OF DISEASE PROGRESSION IN SYSTEMIC SCLEROSIS PATIENTS WITH INTERSTITIAL LUNG DISEASE
Authors: A. Santaniello, C. Bellocchi, S. L. Bosello, E. De Lorenzis, G. Natalello, N. Del Papa, S. Cavalli, D. Benfaremo, G. De Luca, C. Campochiaro, L. Cavagna, V. Codullo, G. Montanelli, A. Severino, M. Caronni, B. Vigone, C. Montecucco, L. Dagna, G. Moroncini, R. Caporali, L. Beretta
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Interstitial lung disease (ILD) is a severe complication of systemic sclerosis (SSc) that may lead to irreversible loss of lung function and increased mortality. Patterns of disease progression (PODs) in SSc-ILD are poorly characterized. <h3>Objectives</h3> To define PODs in SSc-ILD patients that may have clinical implications for patient stratification and clinical trial design. <h3>Methods</h3> Patients with SSc at risk for ILD were recruited in 6 tertiary referral centers. Inclusion criteria were: a) Disease duration &lt; 5 years at the time of the first pulmonary function test (PFT); b) absence of anti-centromere antibodies; c1) diffuse cutaneous subset (dcSSc) OR c2) limited cutaneous subset (lcSSc) with either presence of anti-topoisomerase (Topo I) antibodies or evidence of ILD at high-resolution computed tomography (HRCT). Analyses were restricted to those with ILD at HRCT. PODs at 5 years, defined by absolute changes in forced vital capacity (FVC) % of predictd values, were explored by latent class mixed models (LCMM). Survival analysis (lung-related events) was also conducted on evolution data. <h3>Results</h3> 473 patients at risk for SSc-ILD were identified, of those 424 (89.6%) had evidence of ILD at HRCT and were selected for in-depth analyses. Baseline demographic and clinical characteristics are reported in the Table 1. Multivariable Cox regression showed that FVC values (HR = 0.953, CI95 = 0.956 – 0.982, p &lt; 0.001) as well as the yearly change in FVC (HR = 0.961, CI95 = 0.932 - 0.992, p &lt; 0.05) were predictive of 10-years mortality. LCMM analysis discovered 5 PODs (Figure 1); the majority of patients showed a stable FVC or slow decline in lung function. Patients with sharp improvement had higher age and shorter disease duration compared to patients with sharp deterioration (55 ± 10.5 vs 47 ± 15.3 and 0.88 ± 1.1 vs 1.03 ± 1.5 years, both p &lt; 0.05) and a lower exposure to immunosuppressants (68.4% vs 85.3%); no other difference in clinical or demographic variables was observed among classes. Ten-years survival estimates were lower in patents with sharp (75.1%) or slowly-declining lung function (79.8%) compared to the other groups (&gt;90%) with no event in the sharp improvement class (log-rank p = 8*10-4). The predictive capability of LCMM classes was 0.766 ± 0.03 as measured by Harrel's C-index. <h3>Conclusion</h3> PODs in SSc-ILD are associated with mortality with an increased risk for those with a sharply or slowly declining lung function. The use of PODs for patients' stratification may be useful for prognostication and patient counselling as well as for clinical trial design. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.